Ion therapy guideline (Version 2020)

Charged particle radiotherapy can be traced back to 1954 when Lawrence Berkeley National Laboratory launched proton therapy. After experimentation with different kinds of particles, including neutrons, mesons, helium ions, and neon the Institute Radiological Sciences in Japan started using carbon ions for cancer treatment. Proton therapy has physical advantage Bragg peak, which well realize high-dose distribution tumor target volume low-dose surrounding normal tissue, so found wide applications field ion radiotherapy. Nevertheless, dose biological characteristics are significantly superior those other particles. Compared conventional photon radiotherapy, stands out its favorable radiophysical advantages.1 In current clinical practice, heavy mainly refers So far, although some textbooks publications have provided references standardized there not yet been any consensus guide practices. With rapid development China, increase centers, serves as a promising technology, applicable more indications. guideline practices based on national circumstances situation The Chinese Medical Doctor Association Radiation Oncology Physicians Branch organized domestic relevant experts formulate guidelines reference latest research evidence, should promote popularization application technology benefit majority patients. From point view, photons (Χ-, γ-rays) no charge mass, but such protons charged certain mass. energy release is largest near tissue surface, gradually decreases depth structure. However, will show plateau area initial irradiated maximum energy; that is, deposited reaching tissue. According location size tumor, spread peak modulated accurately cover volume, achieve higher radiation while better protected.2 Due linear transfer difference between they their own characteristics. follows: (i) nearly three-dimensional formed longitudinal transverse directions; (ii) penumbra edge very sharp due deposition track being an approximate straight line; (iii) beam hardly deposits outside far by limiting range.3 compared line, reverse characteristics; multiple scattering effect incident small, also small; flexible, because particles deflect under action magnetic field, flexible diverse systems adopted according actual situation; (iv) medium- high-energy penetrates material, it produce radioisotopes colliding nucleus, decays releases positrons short time, positron emission tomography (PET) used monitor position.4 Protons belong low maintains relative (RBE) radiobiology, properties peak. RBE 1.1-fold rays. Carbon kind high beam, cause ionization density severe DNA damage rate damage, double strand resulting cell mortality. following effects: RBE, generally 2–5-fold rays; lower oxygen enhancement ratio, effectively treat hypoxic tumors resistant less dependence cycle, radiosensitivity S-phase cells Therefore, modes death caused diverse, apoptosis, necrosis, autophagy, premature senility, accelerated differentiation, delayed proliferation, offspring bystander death, on. view aforementioned characteristics, use fewer fractions shorter time cancer.5 range indications, covering almost all types cancers advantages reducing toxicity side-effects suitable children cancer. Because special advantages, prominent superiorities insensitive tumors, re-radiotherapy recurrent sites. existing results, indications summarized follows. Tumors skull base upper cervical spine (chordoma chondrosarcoma);6 Meningioma;7 High-grade glioma.8 Mucosal malignant melanoma;9 Adenoid cystic carcinoma;10 Ocular (choroidal melanoma);11 Intra-orbital tumor;12 Nasopharyngeal carcinoma, radical after recurrence;13 Other tumors: salivary gland ear nasal paranasal sinus cancer, oral on.14 Early peripheral non-small lung carcinoma (NSCLC);15, 16 central NSCLC;17, 18 Oligogenic metastasis or recurrence NSCLC;19 Locally advanced NSCLC.20 Hepatocellular carcinoma;21 Hepatobiliary carcinoma;22 Hepatic metastases (hepatic oligometastasis colorectal cancer);23 Pancreatic cancer;24, 25 Postoperative rectal cancer;26 esophageal still at preliminary study phase, concurrent chemoradiotherapy used.27, 28 Prostate cancer;29 Kidney cancer.30 Sacrococcygeal chordoma;31 Soft sarcoma trunk limbs;32 Osteosarcoma.33 breast stage. patients choose therapy, potential radiotherapy-related adverse reactions.34 side-effects. childhood cancers. Indications nervous system (medulloblastoma, ependymoma, glioma, atypical teratomas/striated muscle craniopharyngioma, germ tumors) non-central (chordoma, chondrosarcoma, rhabdomyosarcoma, Ewing's sarcoma, osteosarcoma, retinoblastoma, lymphoma, neuroblastoma renal tumor).39 It recommended carry tumors. Contraindications relatively few. assessment systemic diseases, status, history however, necessary before Patients conditions candidates Severe heart/lung/liver/kidney/hematological system/nervous diseases complications; Uncontrolled infection sepsis; Routine examination up basic requirements radiotherapy; Advanced anemia, emaciation, electrolyte disorders, coma, cachexia; mental disorders who unable cooperate Extensive metastases; absolute contraindications, massive pleural effusion ascites, perforation risk perforations, bleeding; hollow organs progression; metal prostheses site seriously affect calculation dose. same received during two treatments Serious injury, unhealed skin ulcer, pulmonary fibrosis, luminal narrowing radiation, occurred site. delivery fully utilized successfully implement systems, main techniques, one passive another pencil scanning technique, latter conformability. Many treatment planning currently available Raystation, HIPAN, Xio-N, CiPlan, Syngo. design planning, single-field optimization intensity-modulated (multi-field simultaneous optimization) method selected plan optimization. former robustness, Repeated (rescanning) techniques further accuracy moving targets.40 defined weighted dose, expressed Gy (RBE).41 Dose–volume histograms plans, criteria 95% prescribed line 99% (CTV) 90% volume.42 Computed (CT) images basis design. Given ionizing rays greatly affected densities, important fix requirements. each unit, angle port determine then simulation positioning individualized fixtures.43 supine prone position usually (depending tumors), both hands placed above top head sides body, lateral oblique avoided much possible; require room, chair designed sitting treatment.44 therapeutic bed consider equipment system, allowing table plane rotate around axis. equip rotating cabin, six-dimensional bed, robotic arm bed. motion management could control reduce tissues. Respiratory gating thoracic abdominal At present, respiratory composed sensor, infrared light marker, pressure change monitoring mostly respiration.45, 46 definition carried principle Therapy Group delineation, needs comprehensively considered combination medical patient. image fusion technique enhanced CT, resonance imaging, PET/CT delineate volume. calculated plain CT scan images. Gross (GTV) primary metastatic lymph nodes; CTV includes GTV, subclinical lesions, involved node areas. When delineating CTV, expanded GTV adjusted anatomical barrier. Aside from expanding margin depend setup uncertainty. Ion differs influence Depending boundary 0.3–0.5 cm added side 0.7–1.0 along direction.47 If pattern combined delineated general, radiate radiates boost. There uniform standard limit (OARs) data For hypofractionated early late OAR considered, strictly limited stereotactic body Referring OARs limitation Shanghai, shown Table 1. D1 ≤54 GyE V60 <1%PRV Dmax <45 ≤38.5 V40 <7.66 cc V50 <4.66 <30 ≤31.5 Dmean <6 <8 V55 <5% <36 <25 (bilateral) <20 (unilateral) V20 <0.2 V30 <50% <21 (Bilateral) <18 (Unilateral) <26 <40% <72 <40 GyE(5 GyE/fx) <34 GyE, ≤50% <60 (5 <30% <14 <20% (single lung) V10 V5 ≤30 ≤30% Non-cirrhotic liver, liver MLD GyE; Cirrhosis (Child–Pugh A), <23 ≤18 V12 ≤55% <33% Single kidney, V18 <80%; >20 <10% ≤2% V45 ≤25% V58 <0.03 mL <5 ≤55 V59 V56 ≤60 V54 V50.4 ≤5% <10 ≤45 <1% PRV Low-risk patients: <35% <25% V70 <15% Intermediate-risk <50 <66 D5 D10 Note: constraints prostatic mode 63–66 GyE/20F.54 V65 All devices equipped image-guided system. Cone digital radiography imaging verification, associated online correction. required correct until verified directions <3 mm treatment.42 addition, radioactive isotopes produced collides nucleus substance, emitted period time. PET positron, verify ions. suggested center modes, divided into scanning. Different modes. appropriate lesion Pencil preferred terms conformality accuracy, enabling (IMCT). To many centers without recommended. basically fractionation patterns pediatric recommendations International Consensus Pediatric Tumors.55 variety stages. experience comes Japan. Shanghai Heavy Hospital China explored common various sites listed follows refer (Table 2) 3). Adenocarcinoma, ACC, MMM Chordoma, chondrosarcoma Whole pelvis Primary + positive 36 15 16–19.2 12 5 4 3 4–4.8 P: 56 C: 17.5 2.0 3.5 P X: 60 5.0 50 20 4.0 32 23 8 Tumor lesions 20–22 3.0 4–4.4 Complications consistent incidence serious events than As clarified, record detail timely manner, establish dose–effect relationship collect original data. long-term irradiation closely observed. retina, optic nerve, chiasm, cochlea, parotid gland, brainstem, acute mucositis, prolonged xerostomia, side-effects, radiation-induced brain injury (for example, <3%), improving tolerance quality life Prospective studies indicate grade mucosal reaction nasopharyngeal 11%, 30–40% ≥4 toxicity.56, 57 reports events, approximately 1–7%, most were mild moderate. re-irradiation was reduced (the ≥3 ∼7%).58 pneumonitis early-stage interstitial pneumonitis, locally complications esophagitis. 2 6%, 2%, tracheo-esophageal fistula 2%.59 NSCLC, only 2.1% pneumonitis.60 Concurrent chemotherapy What worth paying great attention shrinkage lead planned esophagus spinal cord behind adaptive especially warranted. complication hepatotoxicity. poor function, reserve previous essential assess function biliary secondary, inflammation hepatic duct stricture (14–28%), gastrointestinal toxicity, may present hemorrhagic duodenitis, ulcers colon, esophagitis (1–7%). close chest wall, rib fractures wall pain syndrome risks adversely patients, median years.61 Gastrointestinal related pancreatic might manifested nausea, vomiting, pain, on, bleeding occur cases. reactions 3–12%. Radiation-induced ulcerative tract pathological symptoms, 51% antral 39% level duodenum.62 prostate enteritis cystitis. results Japanese local seminal vesicles, occurred, genitourinary 2.0% 4.1%, respectively.63 pelvic cystitis.64 Overall, decreasing traditional required. like complications: postoperative incision healing; abnormal growth, bone soft tissue; limb length inequality (those gap 2–6 modified shoes, otherwise surgical correction required); osteoporosis bone; increased fracture; dysfunction joint fibrosis; edema; recall chemotherapeutic drugs; discoloration and/or telangiectasia; secondary second on; lack direct comparison radiotherapy.65 efficacy evaluation cases, baseline Response Evaluation Criteria Solid (RECIST). followed every 3–4 months first years, 6 months. Each follow-up visit include least collection history, examination, examinations (CT, PET/CT, etc., required), laboratory tests, biomarkers. cases included trials, comparing photons. short-term survival recorded detail, paid treatment-related toxicities, provide Members Advisory Panel: Jinming Yu (Shandong Cancer Institute, Shandong First University Academy Sciences), Jiawen Xia (Institute Modern Physics, Guoliang Jiang (Shanghai Hospital). Leader editorial team: Xiaohu Wang & Lanzhou Deputy leaders Jiade Lu Hospital), Ming Chen (Cancer Affiliated Gang Wu (Union Huazhong Science Technology). Review guidance: Ping (Tianjin Lyuhua Hospital, Baosheng Li Yexiong Yong Yin Sciences) writing group (in order surname strokes): Lina (The University), Jin Lin Kong Bing (Guizhou Shuangwu Feng Clinical College Guangying Zhu (China-Japan Friendship Technology), Ruifeng Liu Qiang Kehu Yang (Lanzhou university), Hongzhi Zhang Qiuning Jiayi Ruijin Jingfang Mao Qinyong Hu People's Wuhan Yichao Geng Provincial Xianshu Gao Beijing Xiangkui Mu Hospital)